Diabetes

Question 1

What is a general definition of diabetes?

Answer 1

Chronic hyperglycaemia
Caused by a lack of or diminished efficacy of endogenous insulin
That can cause specific tissue damage over time

Normal ranges for plasma glucose:
Fasting = 3.5-5.6mmol/l
Post prandial = <7.8mmol/l

Question 2

What is the epidemiology of diabetes?

Answer 2

> 90% have type 2
<10% have type 1

Affects 2% of the British population but costs 5-10% of the UK health budget

More common in south Asian or African/afro-Caribbean ethnicities

T2 increases prevalence with age; onset is accelerated by stress, pregnancy, illness and certain other drugs

T2 is also associated with cardiovascular disease risk factors e.g. HTN, obesity, hyperlipidaemia, decreased HDLs

Question 3

What is the aetiology of T1 DM?

Answer 3

Genetic component - 30-50% concordance in MZ twins

Also associated with other autoimmune diseases e.g. hypothyroidism

Other potential triggers for T1 = cold weather (greater initial presentation in winter + more common in colder climates); viruses e.g. measles/mumps/Coxackie B/rotavirus

Question 4

What is the aetiology of T2 DM?

Answer 4

Genetics - play a significant role

Obesity - under activity + overeating (excess triglycerides)

Increases with age

Hx of gestational DM, CV disease or depression

Increased risk if not breast fed until 6m

Question 5

What are some rare causes of diabetes?

Answer 5

Pancreatic

i) Pancreatectomy
ii) Acute/chronic pancreatitis
iii) Trauma
iv) Malignancy
v) Other destruction of pancreas – CF, haemochromatosis

Drug induced

i) Steroids
ii) Thiazides
iii) Anti HIV

Endocrine

i) Cushing’s
ii) Hyperthyroidism
iii) Acromegaly

Others

i) Congenital formation of insulin receptor antibodies
ii) Glycogen storage disease

Question 6

What is the pathophysiology of T1DM?

Answer 6

Immunology:

i) T-cell mediated autoimmune disease → destruction of pancreatic beta cells
ii) First islet antibodies appear in blood during first few years of life - wait until trigger for DM then manifest symptoms within a few weeks

Physiology:
i) Lack of insulin → body perceives lack of glucose →

a) ↓ anabolism → hyperglycaemia (fatigue) →glycosuria, polyuria and thirst (polydypsia) → salt + water depletion → ↑HR + ↓BP (→ death)
b) ↑ catabolism → ↑glyconeolysis, gluconeogenesis and lipolysis (wasting + weight loss) → hyperketonaemia → acidosis (↑RR, ↓BP, ↓T) → diabetic ketoacidosis (→death)
c) ↑ secretion of glucagon, cortisol, GH and catecholamines

Question 7

What is the pathophysiology of T2DM?

Answer 7

Insulin resistance and secretory failure occur for unknown reasons
i) Though patients will have c.50% of beta cells at diagnosis = less extensive than T1

This also helps them avoid DKAs (mostly)

Hyperglycaemic state still present - physiology same as T1

Question 8

How does T1DM present?

Answer 8

Usually acutely:

Polyuria
Polydipsia
Weight loss

DKA

Question 9

How does T2DM present?

Answer 9

Less likely to present acutely with DKA

Asymptomatic - may be a coincidental finding on a blood test

Lack of energy, blurred vision

Question 10

What are some complications that someone with DM may present with?

Answer 10

Staph skin infections Retinopathy
Polyneuropathy Erectile dysfunction
Arterial disease Inflammation of genitals (due to candida infection) Thromboembolism
Hyperosmolar hyperglycaemic state (HHS)

Question 11

How do you investigate and diagnose DM?

Answer 11

Blood glucose tests:
When fasting: >7mmol/L
Random: >11.1mmol/L (on 2 separate occasions)

Oral glucose tolerance test
i) Overnight fast → 75g glucose drink → bloods 2hrs later → >11.1mmol/L = diabetes

Haemoglobin A1C test (HB1AC) - measures average blood glucose over past 2-3 months by examining how much glucose is bound to RBCs - >6.5%/48mmol/mol

Need 2x symptoms + 1 abnormal test for Dx

In young adults - consider LADA- GAD/c peptide/ islet cell antibodies

Question 12

How do you manage T1DM?

Answer 12

Insulin + dietary modification

i) Different injections – short acting, long acting etc

Question 13

What are some different types of insulin and their characteristics?

Answer 13

Human insulin vs. human insulin analogues (vs animal insulin) - both produced using recombinant DNA but the analogues have been modified to add desired characteristics e.g. extended duration

Soluble/short acting insulin: - SC - 15-30mins before meals - onset 30-60mins, peaking at 1-4hrs - duration of c.9hrs
- IV - onset instantaneous - short half life of a few mins (used in DKA)

Rapid acting e.g. Humalog: SC - onset 15mins - lasts 2-5hrs - ideally given just before meals for best control (not after - may hypo)

Intermediate acting e.g. Humalin (NPH or isophane insulins - modified with protamine):
SC - onset 1-2hrs - max effect 3-12hrs - duration 11-24hrs; usually given at bedtime; are cloudy and must be mixed well before injecting

Long acting e.g. Levemir, Lantus: SC - OD - mimic endogenous basal secretion of insulin, lasting up to 36hrs - achieve steady state after 2-4 days = constant low level coverage; usually given at bedtime

Combination preparations e.g. Humulin 70/30 (70units intermediate + 30units short acting):
- Usually short or rapid acting + intermediate, given SC just before a meal (BD/TDS), never at bedtime

Biphasic analogue mixtures e.g. Humalog mix25, Novomix 30:
- Engineered to give a short peak for immediate consumption of food (15 mins after dosing) and a long, broader peak over the next 12-18hrs; never given at bedtime

Question 14

What is hypoglycaemia?

Answer 14

Common side effect of mistiming insulin doses (or not enough food, activity, drinking alcohol = delayed hypo - liver cant release stored glucose)

Presents with:
Autonomic - irritable, hungry, nausea, anxious, sweaty, palpitations, pallor
Neuroglycopaenic - dizzy, confusion, tiredness, headache, visual or hearing problems, poor concentration, odd behaviour, LOC, convulsions

Blood glucose (BG/BM) of <4mmol

Question 15

What is a Diabetic Ketoacidosis/DKA?

Answer 15

Metabolic acidosis + hyperglycaemia + ketonuria

i) During normal feeding/physiology – ketone body production at a minimum
ii) Carbohydrate shortage causes increased production of ketones by liver from the acetyl-CoA from fatty acid oxidation
iii) Limited supply of glucose due to depleted circulating insulin and an increase in fatty acid oxidation due to increased circulating glucagon

The resulting excess ketone body production is more than the tissues can oxidise them and as ketone bodies are acidic (pKa 3.5), blood pH lowers

Question 16

What are the symptoms of a DKA?

Answer 16

Water: Polyuria, thirst; dehydration

GI: Nausea/vomiting; abdominal pain

Limbs: Leg cramps; peripheral cyanosis/cold extremities

Heart: Hypotension; tachycardia

Lungs: SOB; Kussamaul breathing (deep + laboured)
Face: Blurred vision’ acetone smell on breath

Consciousness: Weight loss, weakness; confusion, drowsiness, coma

Question 17

How do you investigate a DKA?

Answer 17

Obs/examination

i) GCS <12
ii) Temp – low (or high if DKA secondary to infection)
iii) Systolic BP <90
iv) HR >100 or <60

Bloods
i) Ketones - >6mmol/L

ABG

i) O2 sats (not on gas) <92%
ii) Bicarb <5mmol/L
iii) pH <7.3; severe if <7.1
iv) hypokalaemia <3.5
v) Raised anion gap

Question 18

What are some triggers for DKA?

Answer 18

Infection - flu, UTI etc

Not following a treatment plan

Injury or surgery

Taking corticosteroids and some other medications

Binge drinking, taking drugs

Pregnancy, having your period

No identifiable trigger

Question 19

How do you manage DKA?

Answer 19

ABC 
i) ?intubate 
ii) Cannulate
iii) Give O2
iv) Catheter 
FOLLOW TRUST PROTOCOLS

Insulin
i) Weight based dose given on a Fixed Rate Intravenous Insulin (???)

Fluids
i) 0.9% NaCl maintenance + rehydration (/48hrs) +/- bolus

Maintenance = special formulas (dont need to know yet)

Rehydration can be worked out empirically from the ABG:
5% dehydrated = +50ml/kg
10% dehydrated = +100ml/kg

Bolus = 10ml/kg - less than in non DKA because at large volume and high rates, there is an increased risk of cerebral oedema in this group (same reason why rehydrated /48hrs not 24)

Monitor and add K as appropriate - K is taken up with insulin – no insulin taken into cells = raised extracellular K

When glucose is <14mmol/L:
- Give 10% glucose 500ml at 50ml/hr +/- KCl depending on levels

Question 20

What do you do if too much K+ is given?

Answer 20

If plasma-potassium concentration above 6.5 mmol/litre there are identifiable ECG changes:

Cardioprotect - Calcium gluconate IV (slow)

Adult:
10–20 mL, calcium gluconate 10% should be administered, dose titrated and adjusted to ECG improvement

(also given in acute hypocalcaemia)

Question 21

What monitoring is needed for DKA?

Answer 21

Standard regular obs

Use blood ketones (not urine) - resolved when <0.6mmol/L and venous pH >7.3

Can also monitor bicarb - but only for first 6hrs as efficacy decreases when IV-ing saline

Question 22

What is a hyperosmolar hyperglycaemic state (HHS)?

Answer 22

High blood sugars (>30mmol/L) → severe dehydration → increase in blood osmolarity → coma, death

Different from DKA:
Metabolic acidosis is absent or mild
Delirium is more common

Treatment:

i) Correct dehydration with IV fluids
ii) Reduce blood sugar with insulin

Question 23

What are sick day rules for DM?

Answer 23

Guidelines given by diabetes care team advising what to do with insulin and monitoring etc during a period of illness that does not require admission to hospital

Baseline insulin doses may need adjusting

Glucose monitoring and results recorded increased in frequency - every 3-4hrs, sometimes every 1-2 - these results will then also affect how insulin doses are titrated subsequently

Consider ketone monitoring (blood or urine) - every 3-4hrs, sometimes every 1-2, including through the night; urine ketones greater than 2+ or blood ketones >3mmol/L then person should contact GP or diabetes care team ASAP (as we want to avoid full blown DKA)

Maintain normal eating pattern as close as possible even when appetite reduced; meals can be replaced with carbohydrate rich drinks e.g. juices, sugary drinks, milk etc

3L/5pints of fluid should be drunk; if vomiting or diarrhoea persistent then medical advice should be sought as IV fluids may be needed

When recovered - should continue to monitor BG carefully until normalises

Question 24

What are macrovascular complications of DM?

Answer 24

Atherosclerosis

i) Stroke
ii) MI
iii) Gangrene → amputation

Also - infection might not look like infection in an ischemic foot as insufficient inflammatory markers are flowing to the area

Question 25

What is a Charcot foot? How is it investigated and managed?

Answer 25

Acutely:

• A painful red swollen foot in a patient with diabetic neuropathy
• Deformity e.g. ‘rockerbottom feet’
• Loss of function
• Can be painful but surprisingly little/absent - especially given the extent of joint destruction

Investigation:

• Neurovascular assessment of the foot and ankle
• HbA1C testing
• Plain 2 view XR = evidence of bony deformity +/- osteomyelitis (e.g. periosteal reaction)
• MRI (more sensitive for soft tissue or early stage osteomyelitis)

Management:

• Education re. joint damage and DM control
• Immobilisation - with a cast, for 3-6/12 with repeated XR
• Possible use of bisphosphonates
• Surgery - for severe/unstable deformity that if untreated will result in amputation
• Follow up podiatry with special orthotics for life

Healing process takes c.1-2yrs
- Prevent trauma, note temperature changes, check feet daily etc

Manage any complications:
- Fractures, neuropathic ulcers +/- infection/osteomyelitis; amputation

Question 26

What is diabetic retinopathy?

Answer 26

i) Thickening of basement membrane and increased permeability of retinal arteries → occlusion, aneurysm formation, increased exudates

Blindness is common

Question 27

What is diabetic nephropathy?

Answer 27

Glomerular damage

Ischemia of afferent/efferent arterioles

Ascending infection
i) Diabetic immunity often compromised – more susceptible to UTIs

Renal hypertrophy

Albuminurea – first detectable marker of diabetic nephropathy

Question 28

What is diabetic neuropathy?

Answer 28

Unsure aetiology (?)

Types:
i) Symmetrical mainly sensory = stocking and glove disruption

ii) Acute painful = shins, worse at night
iii) Mononeuropathy and mononeuritis multiplex = CN3+6 and carpal tunnel
iv) Diabetic amyotrophy = progressive wasting of muscle tissue
v) Autonomic neuropathy = CV and bladder problems, ED

Question 29

What is the pathophysiology behind many of the complications?

Answer 29

Related to the duration and degree of hyperglycaemia – good control = fewer complications

Glycation = addition of a sugar to a lipid through non-enzymatic means, leads to the accumulation of AGE’s (advanced glycation end-product) which are implicated in cell damage and inflammation
i) Excess sugar means more AGE’s and greater negative effects

Cells of retina, kidney and nerves do not require insulin for glucose uptake
i) Excess glucose enters cells (excess glycation etc)

Polyol pathway = excess glucose not put into the TCA cycle will be converted into sorbitol → fructose

i) These cannot exit cells so draw water and other ions in down electrochemical gradients → affects cell functioning
ii) Also produces ROS → direct cell damage Microvascular damage
i) Narrowing of vessels → reduction in nutrients and oxygen
ii) Accelerated by release of excess growth factors (VEGF) → more damage through over proliferation

Question 30

How is T2DM managed?

Answer 30

First line = Diet + Exercise - can reverse a pre-diabetic state in this way

Potential for:

i) Metformin
ii) Sulfonylurea
iii) ‘Glitazones’
iv) Insulin

Question 31

What is prediabetes?

Answer 31

A state of impaired glycaemic control

Categorised by:
Fasting glu = <7.0mmol/l
Post OGT 7.8-11.0mmol/l
HbA1c = 5.7-6.4%

Question 32

Need more stuff on drugs and side effects

Answer 32

Metformin SE: N+V+D, stomach cramps, loss of appetite

Question 33

What monitoring in DM is required?

Answer 33

Blood glucose

• Self monitoring via finger prick test for those taking insulin
• e.g. 4x per day (before each meal and once before bed, but depends on regimen and personal factors)
• Increase monitoring during times of illness and watch for hyperglycaemia

HbA1C – targets are variable:
- e.g. 6.5%/48mmol for those on monotherapy with metformin, but increases slightly if on dual or triple therapy

Blood ketones
- Home blood monitor (NOT URINE, as less sensitive)

BP:

• At least once a year
• Aim for 135/85

Weight:

• Kept low/reduced
• Reinforce dietary control

Eyes:
- At least once yearly checks for diabetic retinopathy

Kidneys:
- At least once yearly U+Es for albumin:creatinine and eGFR

Feet:
- At least once yearly podiatry review by specialist service

Medication:
- Understanding, adherence, side effects etc

Question 34

What other professionals are involved in DM management?

Answer 34

Dieticians – carb counting

Endocrinologists – long term management

Diabetes specialist nurses – how to insulin, how to self-monitor, hypo/hyper management

Podiatrists – foot care

Ophthalmologists - eye care

Question 35

More precisely, what are patterns of inheritance for T1DM?

Answer 35

If X has DM:
Mother - 2% (though in mothers that develop DM before age 8 - same transmission risk as fathers) 
Father - 8% 
Both parents - 10%
Sibling - 10%
DZ twin - 15%
MZ twin - 40%

Specific genetics - c.20 known associated e.g. HLADR3, HLADR4

Question 36

More precisely, what are some patterns of inheritance for T2DM?

Answer 36

If either mother or father has T2 then risk increases 15%

If both have T2 then risk increases by 75%

MZ twins - 10%
DZ twins - 90%

Thus more heritable than T1, though still not entirely genetically determined

Question 37

What is the pathophysiology of T1DM initial presentation?

Answer 37

1) Insulin deficiency + glucagon excess
2a) increased blood ketones - vomiting, acidosis, osmotic diuresis
2b) increased blood glucose - osmotic diuresis
3) fluid and electrolyte depletion - cellular dysfunction, shock, cerebral oedema

Question 38

How do you manage a mild hypo?

Answer 38

Check blood glucose to confirm symptom profile

If conscious and patient able to swallow:

3-5 glucose tablets; 100-200mls fizzy drink/juice

Wait 10 mins - if no response - repeat

F/U with longer acting carb e.g. bread or biscuit

Check BG in 15mins

Question 39

How do you manage a moderate hypo?

Answer 39

As for mild if possible, if too unwell to cooperate:

0.5-1 tube of glucogel

Wait 10 mins - if no improvement repeat

F/U with longer acting carb, check BG in 15mins

Question 40

How do you treat a severe hypo?

Answer 40

At this point patient has a reduced level of consciousness +/- fitting:

• do not attempt give anything PO

With venous access:
- 10% glucose with giving set, 50ml boluses

Without IV access

• Glucagon - SC or IM injections
• If <5yrs = 0.5mg
• If >5yrs = 1mg

Wait 10mins

When conscious - follow mild regimen

Question 41

What is hypo unawareness?

Answer 41

When people are frequently unable to notice when they are hypoing - puts them at risk of severe hypos + being in risky situations to hypo e.g. driving, crossing roads, cooking

Common in people with T1 who have had it for a number of years; also common if have hypo’d recently within the last 2days; stress, depression and alcohol

Also associated with certain medications e.g. beta blockers

Managed with education and mindfulness; if frequent, may also be asked to increase window of glycaemic control - elevating target BG range (poss by changing how one uses insulin) prevent frequently dropping too low

Question 42

What is reactive/rebound hypoglycaemia?

Answer 42

Is postprandial hypoglycaemia - low blood sugar that occurs after a meal, usually within 4hrs of eating

Cause for most is unknown - may depend on types of food or individual physiology/gut motility; also alcohol, surgeries e.g. for an ulcer, inherited metabolic disorders etc.

Medical evaluation required to see if symptoms definitely reactive hypos; any known underlying cause corrected; ensuring you eat a balanced diet - all food groups, avoid sugary and processed carbohydrates e.g. white bread/pasta - esp on an empty stomach; eat food when you drink alcohol; snacking; insulin dose may need readjusting

Question 43

What is the Somogyi phenomenon?

Answer 43

Post hypoglycaemic hyperglycaemia

Can be acute or chronic

May be the result of high blood sugar in the morning due to excess insulin at night (too much insulin may make diabetes management unstable)

Possible mechanism: prolonged hypo - physiological stress - glucagon + cortisol + adrenaline release - temporary insulin resistance - hyperglycaemia

Rigorous BG monitoring including at night will help understanding - may need to readjust night doses

Question 44

What is the Dawn phenomenon?

Answer 44

Different to - though often confused with - Somogyi rebound

Early morning increase in blood glucose occurring between 8-10 hours of sleep secondary to cortisol/adrenaline/glucagon release and subsequent hyperglycaemia (so same mechanism but this one is sleep related whereas Somogyi doesn’t have to be sleep related)

Question 45

What is the prognosis for individuals with diabetes?

Answer 45

Life expectancy reduced by 23 years

DKA - 10x bigger killer than hypos

30-40% develop microalbuminaemia
25% require laser surgery for retinopathy

Complications are worse for paediatric T2

25% of patients will have an amputation in their lifetime

Question 46

How do you manage exercise and hypos?

Answer 46

Prevent hypo during exercise:

• reduce insulin with meal before exercise = lower insulin conc. during and higher starting BG, less of a drop during (though hyper or delayed onset hypo may still occur later)
• high intensity exercise burst - 10s intermittently throughout session or to top/tail= increase in adrenaline, raised glucose during and after exercise (may still late onset hypo)

Post exercise - body is more sensitive to insulin (very sensitive within first 2hrs, waning over 48+hrs) - so increase potency of exogenous insulin and subsequent greater glu uptake

Prevent hypo after exercise:

• eat properly after
• reduce insulin with meal after exercise = less insulin during ‘hot spot’ of insulin sensitivity, stable BG for c.8hrs (may be hyper or delayed hypo)
• reduce basal insulin and insulin before and after exercise = less insulin to compensate for increased sensitivity, normal glucose during sleep without excessive carb intake and more stable glucose next day (working out reduction dose may require trial and error)

Question 47

What are the rules for driving and hypos?

Answer 47

Need to have a BG of above 5 to drive - mornings can be hard sometimes - need to make sure you eat breakfast

If hypo when driving - have to stop and wait 45 mins + BG of over 5 before they can drive again

Question 48

more cards to update/add

Answer 48

t’s worthwhile thinking of the average patient who is taking metformin for T2DM, you can titrate up metformin and encourage lifestyle changes to aim for a HbA1c of 48 mmol/mol (6.5%), but should only add a second drug if the HbA1c rises to 58 mmol/mol (7.5%)

Dietary advice
encourage high fibre, low glycaemic index sources of carbohydrates
include low-fat dairy products and oily fish
control the intake of foods containing saturated fats and trans fatty acids
limited substitution of sucrose-containing foods for other carbohydrates is allowable, but care should be taken to avoid excess energy intake
discourage the use of foods marketed specifically at people with diabetes
initial target weight loss in an overweight person is 5-10%

HbA1c targets

This is an area which has changed in 2015
individual targets should be agreed with patients to encourage motivation
HbA1c should be checked every 3-6 months until stable, then 6 monthly
NICE encourage us to consider relaxing targets on ‘a case-by-case basis, with particular consideration for people who are older or frail, for adults with type 2 diabetes’
in 2015 the guidelines changed so HbA1c targets are now dependent on treatment:

Lifestyle or single drug treatment

Management of T2DM HbA1c target
Lifestyle 48 mmol/mol (6.5%)
Lifestyle + metformin 48 mmol/mol (6.5%)
Includes any drug which may cause hypoglycaemia (e.g. lifestyle + sulfonylurea) 53 mmol/mol (7.0%)

Practical examples
a patient is newly diagnosed with HbA1c and wants to try lifestyle treatment first. You agree a target of 48 mmol/mol (6.5%)
you review a patient 6 months after starting metformin. His HbA1c is 51 mmol/mol (6.8%). You increase his metformin from 500mg bd to 500mg tds and reinforce lifestyle factors

Patient already on treatment

Management of T2DM HbA1c target
Already on one drug, but HbA1c has risen to 58 mmol/mol (7.5%) 53 mmol/mol (7.0%)

Drug treatment

The 2015 NICE guidelines introduced some changes into the management of type 2 diabetes. There are essentially two pathways, one for patients who can tolerate metformin, and one for those who can’t: SEE DIAGRAMS

Tolerates metformin:
metformin is still first-line and should be offered if the HbA1c rises to 48 mmol/mol (6.5%)* on lifestyle interventions
if the HbA1c has risen to 58 mmol/mol (7.5%) then a second drug should be added from the following list:
sulfonylurea
gliptin
pioglitazone
SGLT-2 inhibitor
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then triple therapy with one of the following combinations should be offered:
metformin + gliptin + sulfonylurea
metformin + pioglitazone + sulfonylurea
metformin + sulfonylurea + SGLT-2 inhibitor
metformin + pioglitazone + SGLT-2 inhibitor
OR insulin therapy should be considered

Criteria for glucagon-like peptide1 (GLP1) mimetic (e.g. exenatide)
if triple therapy is not effective, not tolerated or contraindicated then NICE advise that we consider combination therapy with metformin, a sulfonylurea and a glucagonlike peptide1 (GLP1) mimetic if:
BMI >= 35 kg/m² and specific psychological or other medical problems associated with obesity or
BMI < 35 kg/m² and for whom insulin therapy would have significant occupational implications or
weight loss would benefit other significant obesity-related comorbidities
only continue if there is a reduction of at least 11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months

Practical examples
you review an established type 2 diabetic on maximum dose metformin. Her HbA1c is 55 mmol/mol (7.2%). You do not add another drug as she has not reached the threshold of 58 mmol/mol (7.5%)
a type 2 diabetic is found to have an HbA1c of 62 mmol/mol (7.8%) at annual review. They are currently on maximum dose metformin. You elect to add a sulfonylurea

Cannot tolerate metformin or contraindicated
if the HbA1c rises to 48 mmol/mol (6.5%) on lifestyle interventions, consider one of the following:
sulfonylurea
gliptin
pioglitazone
if the HbA1c has risen to 58 mmol/mol (7.5%) then a one of the following combinations should be used:
gliptin + pioglitazone
gliptin + sulfonylurea
pioglitazone + sulfonylurea
if despite this the HbA1c rises to, or remains above 58 mmol/mol (7.5%) then consider insulin therapy

Starting insulin
metformin should be continued. In terms of other drugs NICE advice: ‘Review the continued need for other blood glucose-lowering therapies’
NICE recommend starting with human NPH insulin (isophane, intermediate-acting) taken at bed-time or twice daily according to need

Risk factor modification

Hypertension
blood pressure targets are the same as for patients without type 2 diabetes (see table below)
ACE inhibitors or angiotensin II receptor blockers (ARB) are first-line
an ARB is preferred if the patient has a black African or African–Caribbean family origin

Clinic BP ABPM / HBPM
Age < 80 years 140/90 mmHg 135/85 mmHg
Age > 80 years 150/90 mmHg 145/85 mmHg

Antiplatelets
should not be offered unless a patient has existing cardiovascular disease

Lipids
following the 2014 NICE lipid modification guidelines only patients with a 10-year cardiovascular risk > 10% (using QRISK2) should be offered a statin. The first-line statin of choice is atorvastatin 20mg on

Question 49

How do you manage hypos from sulphonylurea’s (gliclazide, tolbutamide)?

Answer 49

Drugs increase insulin release from islet cells so there is potential for hypos

Hypos may last 24-48hrs due to drug half life

10% glucose infusions may be required continuously during this time - 100mls/hr - after the initial period of unconsciousness is treated

If initial BG <1.3mmol/L - omit further doses until diabetes team R/V

If initial BG 3-3.9mmol/L and not explained by a missed meal - reduce usual dose by 50%

Question 50

What are some typical regimens of insulin dosing?

Answer 50

Basal-bolus:
- Quick acting insulin before meals + 1-2 medium/long acting insulins daily

Twice daily:
- Insulin mixtures BD; often with metformin in T2DM

Once daily:
- T2DM - Medium or long -acting insulin at bedtime together with oral hypoglycaemic agents

Question 51

What are the names, mechanisms and side effects of the drugs used in T2DM?

Answer 51

Metformin: (500mg OD with breakfast)

• Decreases gluconeogenesis and increases peripheral utilisation of glucose; since it acts only in the presence of endogenous insulin it is effective only if there are some residual functioning pancreatic islet cells
• SE: abdo discomfort, N+V; lactic acidosis, hepatitis; safe in pregnancy; avoid if eGFR <30; U+E annually

Sulfonylureas:

• e.g. gliclazide
• Increase insulin secretion
• SE: hypoglycaemia, GI discomfort; agranulocytosis; avoid in pregnancy

Gliptins:

• e.g. lina’gliptin’
• (dipeptidylpeptidase-4-inhibitors)
• Increase insulin secretion and lower glucagon secretion

Pioglitazone:

• (a thiazolidinedione)
• Reduces peripheral insulin resistance
• Several long term risks e.g. heart failure (CI) bladder Ca (CI)
• SE: bone #, weight increase, visual impairment; avoid in pregnancy

SGLT-2 inhibitors:

• e.g. Canagli’flozin’
• Reversibly inhibits Na-Glu transporter in PCT, reducing glucose reabsorption/increasing excretion
• SE: UTI, DKA, hypoglycaemia, fornier’s gangrene (genital/perianal nec fasc…)

Glucagon-like peptide-1 receptor agonists:

• e.g. Liraglu’tide’
• Binds to this receptor - stimulating insulin secretion, suppressing glucagon secretion and slowing gastric emptying

Question 52

What is a typical escalation pathway for management in T2DM?

Answer 52

1) Diet/lifestyle:
- Low sugary foods, low fatty foods
- Increase fibre intake, increase low fat dairy and oily fish
- Aim to lose 5-10% of weight if overweight

2) Add metformin
3) Add one of: sulfonylurea OR pioglitazone OR gliptin OR SGLT-2 inhibitor
4) Add an additional one off the list
5) Metformin + sulfonylurea + GLP-1 mimic OR metformin + insulin regimen (e.g. NPH)